Search

It is well documented that MGAT5 (Glycosyltransferase V) products are over expressed in carcinomas and likely accelerate metastasis by promoting neoangiogenesis. We now report a similar over expression in primary osteoblastic osteogenic sarcoma and demonstrate new intratumoural blood vessels. Expansion of the tumours is by osteoclastic resorption of both trabecular and cortical bone with the latter by cutting channels similar to physiological cutting cones. Osteoclasts, adjacent capillaries, and related mast cells also overexpress MGAT5 products and we speculate that this facilitates neoangiogenesis.

We have studied the impact of primary central conventional chondrosarcoma on the bone tissues (trabecular, endosteal and cortical) of the proximal femur. A combination of macroscopy, contact radiography, histology, lectin histochemistry and immunohistochemistry techniques were employed. The tumours expanded by driving the resorption of bone tissue progressively removing trabecular, endosteal and cortical bone ultimately causing pathological fracture of the latter. Resorption of all tissue types was by osteoclasts invariably accompanied by companion mesenchymal tissue containing capillaries, mononuclear cells and mast cells. There were no new pathological mechanisms in play, rather the usurpation of normal physiological mechanisms of bone tissue remodelling and modelling. Lectin histochemistry showed that osteoclasts, endothelial cells and mast cells expressed GnTase V (MGAT5) which has been implicated in neoangiogenesis. The linkage of osteoclasts and new blood vessels we believe is key to successful bone resorption.

Chondro/osteoclasts and mast cells are cells of interest in the cartilage and bone destruction of joints affected by rheumatoid arthritis (RA). Both are major cellular components of the vascular synovial pannus proliferation characteristic of this disease. Chondroclasts degrade calcified cartilage and osteoclasts degrade bone tissue. Chondroclasts and osteoclasts are identical cell types and differentiate from monocyte precursors. Our studies show a close microanatomical relationship between these cells and new capillary formation (shown by the lectinPsophocarpus tetragonolobus– PTL-11) in the resorption sites of the mineralized tissues. Clast and mast cells express receptors for the lectin lPHA indicating beta1,6-acetylglucosaminal transferase V (GNTase V/MGAT5) activity providing a mechanism for neoangiogenesis. In addition to an angiogenetic function for mast cells it is probable that their products control monocyte differentiation and chondro/osteoclastogenesis.

Lectin staining of benign and malignant cartilage proliferations indicates restricted glycoprofiles and significant differences. In general terms benign lesions show less cellular binding and more matrical binding than malignant lesions. This suggests that in the benign category cells are less metabolically active and the matrix more structurally stable. Chondrosarcoma cells stain with the lectin lPHA indicating increased β1-6 branching linkages in complex N-linked glycans which is also a known feature of carcinoma cells. Increased angiogenesis and increased mast cell numbers are present in the connective tissue septa separating lobules of chondrosarcoma. The blood vessels stain with the lectins PTL-II and lPHA. Mast cells stain with lPHA.β 1-6 linkage is initiated by the Golgi-bound glycosyltransferase GnTase V. Increased β1-6 linkages are believed to enhance the metastatic potential of a malignant cell by angiogenesis. LPHA ligand is present not only in chondrosarcoma cells but also in endothelial cells and mast cells of the septa.The ligand for the lectin PTL-II is a core 1 O-linked glycans produced under the auspices of the galactosyltransferase T synthase. Production of this glycans by endothelial cells is believed to be obligatory for the formation of these cells into tubes as part of the construction of functioning blood vessels.There are, therefore, two candidate genes in chondrosarcoma worthy of further study viz those for GnTase V and T synthase. Targeted disruption of the activities of these genes has therapeutic possibilities.

Both climate scientists and non-scientists (laypeople) attribute extreme weather events to various influences. Laypeople’s attributions for these events are important as these attributions likely influence their views and actions about climate change and extreme events. Research has examined laypeople’s attribution scepticism about climate change in general; however, few climate scientists are familiar with the processes underpinning laypeople’s attributions for individual extreme events. Understanding these lay attributions is important for scientists to communicate their findings to the public. Following a brief summary of the way climate scientists calculate attributions for extreme weather events, we focus on cognitive and motivational processes that underlie laypeople’s attributions for specific events. These include a tendency to prefer single-cause rather than multiple-cause explanations, a discounting of whether possible causes covary with extreme events, a preference for sufficient causes over probabilities, applying prevailing causal narratives, and the influence of motivational factors. For climate scientists and communicators who wish to inform the public about the role of climate change in extreme weather events, these patterns suggest several strategies to explain scientists’ attributions for these events and enhance public engagement with climate change. These strategies include showing more explicitly that extreme weather events reflect multiple causal influences, that climate change is a mechanism that covaries with these events and increases the probability and intensity of many of these events, that human emissions contributing to climate change are controllable, and that misleading communications about weather attributions reflect motivated interests rather than good evidence.

Mast cells and angiogenesis play roles in the synovium of both osteoarthritis and rheumatoid disease but precise mechanisms are unclear. In a study of the glycome of human synovial biopsies from normal, osteoarthritic and rheumatoid disease cases mast cell numbers were increased in both osteoarthritic and rheumatoid disease synovial samples (the latter more than the former). Both mast cells and endothelial cells expressed receptors for the lectinPhaseolus vulgarisleukagglutinin (lPHA). Endothelial cells only expressed receptors forPsophocarpus tetragonolobus(PTL-II). Mast cells and angiogenesis are, therefore, likely to have a common pathogenetic mechanism in osteoarthritis and rheumatoid synovitis, the difference being one of degree. lPHA receptor expression in both mast cells and endothelial cells indicates βl,6N–acetylglucosaminyl (GlcNAc) – transferase V (GnTaseV/MGAT5) activity. This provides a linkage between mast cells and endothelial cell proliferation. Endothelial cells show core 1 O-glycosylation (positive PTL-II staining) which is probably necessary for the formation of competent tubular structures and for continuing vascular integrity.

Perceptual discrimination requires the ability to determine that two stimuli are different. It is well established that neuronal representations in sensory cortices (i.e. the specific neuronal activity patterns evoked by the stimuli) are essential for perceptual choice 1–4. Yet, the general principles by which those representations are compared in sensory systems remain paradoxically elusive. Indeed, the resolution of the neuronal representations is an order of magnitude more precise than the discrimination capabilities of the animals during behavioral tasks 5–9. This large discrepancy between theoretical neural resolution and actual animal discrimination threshold suggests that the integrative mechanisms leading to perceptual decision are computationally limited. To determine those computational constraints, we recorded the activity of layer 2/3 neurons in the primary visual cortex (V1) of mice performing a Go/NoGo orientation discrimination task. We found that two oriented cues were perfectly perceived as distinct when there was no overlap between their neuronal representations. However, at the limit of discriminability, V1 activity stopped encoding for the orientation of the visual stimulus. Instead, we observed a funneling of the V1 activity toward distinct domains of the orientation representation space, likely generated by an orientation-dependent modulation of the neuronal excitability. The relative neuronal activity at those domains provided a probabilistic indication that the stimulus belonged to the Go or NoGo category. Thus, the categorical classification by V1 of the presented stimulus predicts accurately the probabilities of the animals’ perceptual decisions.

Comparatively little is known about the glycome (the set of glycans and glycoconjugates made by the cell, tissue or organism) of bone and cartilage. The glycome has a high-density coding capacity and is important in post-translational modification. Lectin histochemistry provides insights into the glycome and we applied this technique to an ectopic ossification site in human bronchial cartilages.Our results show that cartilage matrix at the site of erosion by chondroclasts has a limited but definite glycoprofile. In contrast, bone matrix does not express many lectin ligands. Chondroclasts have an extensive glycoprofile similar to that of, but not identical to, osteoclasts. N and O glycans are both expressed in the zone of presumptive mineralization and are relevant to that process. Bone trabecular lining cells communicate with osteocytes via intracanalicular processes and some lectin ligands were expressed by these three components.Mast cells and angiogenesis were prominent. Since cartilage normally resists vascular penetration by the secretion of antiangiogenesis factors it is postulated that the hypertrophic chondrocytes in the mineralization zone produce proteases which inhibit antiangiogenesis and facilitate angiogenesis by mast cells.